Arterial spin labeling (ASL) has proven its ability to non-invasively measure cerebral blood flow (CBF). However, widespread use of this promising technique has been prevented by its long acquisition time due to the inherently image low signal-to-noise ratio (SNR). Recently, it has been shown that the use of 3D instead of 2D 'single-shot'sub-second imaging sequences greatly improve SNR and slice coverage of the brain. The new generation of MRI scanners equipped with improved magnetic gradient systems, phased array multi-channel receiver systems and high magnetic field strengths (3T and 4T) greatly enhance the performance of the ASL pulse sequences. Clinical use of state-of-the-art ASL techniques is very limited since no major MR scanner manufacturer supports this type of perfusion imaging, with currently no commercial ASL products available on any MRI scanners. We are proposing the development of a family of highly efficient 3D MRI pulse sequences for perfusion imaging using ASL and CPMG spin echo pulse sequences, gradient-and-spin-echo (GRASE). This pulse sequence set will consist of single-shot (one set of repeatedly refocused signals) and multi-shot acquisitions using advanced variants of ASL blood labeling preparation schemes. The sequences will be designed and implemented on a 1.5T MR scanner equipped with a 40 mT/m high performance gradients. The new imaging sequences will be ported to 3T and 4T high field scanners at different universities, Washington University, University of Pennsylvania, University of California San Francisco and Harvard where the new imaging technology will undergo further optimization and testing. The availability of these highly efficient pulse sequences to researchers and clinicians will give the capability to perform 3D perfusion imaging of the whole brain at conventional high resolution 256 x 256 matrix images and to perform time averaged sub-second 3D perfusion maps which differentiate different vascular territories. The resulting quantitative measures of blood perfusion will be useful for studies of neurodegenerative diseases, drug trials and identifying perfusion abnormalities in stroke and cerebrovascular disease.